My long-term goal is to understand the mechanisms used by animal viruses in taking over the protein synthesis machinery of infected cells. I plan to use two representative viral systems in this study, vesicular stomatitis virus (VSV) and poliovirus. These are model systems representing the rhabdoviruses, which have a negative strand RNA genome, and picornaviruses, which have a positive strand RNA genome. I hope to be able to decipher the structural signals in the viral mRNAs which make them more efficient than cellular mRNAs. Three major projects are contemplated: 1) I plan to continue my nucleotide sequencing studies on the ribosome recognition sites in the five VSV mRNAs, three of which I have already sequenced. Then further studies will be directed a) toward examining possible functions of the variety of modifications on the 5'-end of VSV mRNAs, b) developing ribosome binding conditions which are completely specific for the proper initiation sites, and c) defining what features of the ribosome recognition sequences are responsible for making VSV mRNAs highly efficient. 2) I plan to determine the nucleotide sequence of the ribosome binding site on poliovirus mRNA. This RNA appears to be unique in that it is a highly efficient mRNA which lacks a capped and methylated 5' terminus. These studies will be directed toward analyzing what role the 5' terminal protein which is present on the virion RNA (but not on functional mRNA) might play in translation. Such studies will require that the ribosome binding analyzed is shown to be specific for the initiation site. 3) Once highly specific ribosome binding assays are developed, I plan to use them to analyze the ability of VSV mRNA and polio mRNA to compete with cellular mRNA for ribosome binding and for translation under a variety of conditions. Such competition may be directly relevant to the mechanism of shut-off of host protein synthesis after viral infections.